Immunosuppressant therapy (IST) non-adherence is the leading cause of preventable graft (transplanted kidney) loss among renal transplant recipients (RTRs). There is a critical gap in the knowledge on how to implement effective interventions for RTRs to improve adherence and thus optimize clinical outcomes. Given our long-term goal to optimize therapeutic success and minimize adverse clinical outcomes in RTRs, the objectives of this proposal are to address this gap in the knowledge through: (1) designing, implementing, and evaluating a patient-specific behavioral contract-based intervention to improve RTRs'IST adherence rates (contracts will be written, signed agreements between the RTR and healthcare provider in which the RTR agrees to be adherent to IST according to mutually agreed upon criteria);and (2) measuring the effects of IST adherence on RTRs'health-related quality of life (HQoL) and healthcare costs. Research suggests that: (1) behavioral contracts utilizing sound theoretical underpinnings have successfully improved adherence (compliance) to medical treatment among many diverse populations (however, behavioral contracts have not been studied as an IST adherence intervention with RTRs);(2) IST non-adherence increases risk of graft rejection;and (3) adherence to medication therapy lowers healthcare costs and improves HQoL (however, the relationships between IST adherence, healthcare costs, and HQoL have not been studied in RTRs). The rationale for the study is that, once it is better understood how to implement effective IST adherence intervention programs, clinicians will have a valuable tool to promote therapeutic success, improve HQoL, and reduce healthcare costs. Therefore, in this project, we will pursue the following three Specific Aims: (1) determine the effectiveness of an IST adherence contract-based intervention on IST adherence;(2) determine the relationship between IST adherence, the intervention, and RTRs'HQoL;and (3) determine the influence of IST adherence and the intervention on RTRs'healthcare costs. To achieve the Specific Aims, a randomized controlled trial of the patient-specific behavioral contract-based intervention will be conducted, and data regarding adherence, HQoL, and healthcare costs will be collected over a 12-month period for each RTR study participant and analyzed. This project will thus facilitate NIH's mission of promoting healthy lives, increasing well-being, and reducing burden of illness and disparity by providing data regarding an effective adherence intervention targeting RTRs and the impact of IST adherence and the behavioral contract intervention on RTRs'health and economic outcomes and HQoL. Collectively, this new knowledge will provide critical steps toward optimizing RTRs'graft maintenance, productivity, and HQoL, while decreasing graft rejection, return to dialysis, morbidity, mortality, and healthcare costs. The application of the new knowledge gained in this project will also help to more effectively utilize kidneys donated for transplantation by improving adherence, health, and economic outcomes. Public Health Relevance: This project will facilitate NIH's mission of promoting healthy lives, increasing well-being, and reducing burden of illness and disparity by providing data regarding: (1) an innovative immunosuppressant therapy adherence intervention targeting renal transplant recipients;and (2) the impact of immunosuppressant therapy adherence on renal transplant recipients'health and economic outcomes and health-related quality of life. Collectively, this new knowledge will provide critical steps toward optimizing recipients'transplanted organ maintenance, productivity, and health-related quality of life, while decreasing graft rejection, return to dialysis, morbidity, mortality, and healthcare costs. The application of the new knowledge gained in this project will also help to more effectively utilize kidneys donated for transplantation by improving adherence, health, and economic outcomes.